Table 2.

New proposals of holistic treatments to contrast neuroinflammation in glaucoma.

New therapies	Authors	Upregulation	Downregulation
Antioxidants: Tempol	Yang et al. (72)	IL-13, IL-4, IL-6	Modulation of NF-κB signaling: decrease of TNF-α, IFN-γ, IL-1β, IL-2, IL-1α
Ketogenic diet	Harun-Or-Rashid et al. (73); Lu et al. (74); Shimazu et al. (75)	- Activation of Nrf2 - Increase of anti-inflammatory agents IL-4 and Arginase-1 - Increase of hydroxycarboxylic acid receptor 1 (HCAR1) - Increased levels of Arrestin β-2 protein, required for HCAR1 signaling - Increased GABAergic output and lowered presynaptic excitatory neurotransmitter release - Stimulation of HCAR2	Inhibition of - AMPK phosphorylation - Iba1 expression - NLRP3 inflammasome HCAR1-mediated - Oxidative stress by increased FOXO3A and MT2 activity - Class I histone deacetylases - NF-κB p65 nuclear translocation
Coriolus Versicolor and Hericium Erinaceus (Mushrooms)	Trovato Salinaro et al. (76)	IL-6, interferons immunoglobulin G, macrophages, T-lymphocytes, expression of Hsp70, TRX, HO-1	- Increase of Lipoxin A4 (endogenous eicosanoid) which blocks the production of pro-inflammatory mediators (ROS/RNS) - Stimulation NGF synthesis: modulation of cholineacetyltransferase + acetylcholinesterase
Hydrophilic Saffron extract (Crocus sativus)	Fernandez-Albarral et al. (77)	Inversion of OHT-induced down regulation of P2RY12	- Reduction of morphological signs of microglia activation - Reduction of various neurotoxic molecules (TNF-α, IL-β) - Suppression caspase-3 and caspase-9 activities: prevention of retinal ganglion cell death - Reduction of ROS: increase of blood flow in the retina and choroid